The goal of the proposed research is to understand the role of spontaneous activity in early cortical development. The cortex is spontaneously active from the first moments when circuits form. However, so far we know only very little about the patterns of spontaneous activity in the early cortex and very few models have addressed their role in shaping its circuitry. An experimental neuroscientist from the Max Planck Florida Institute (MPFI) is teaming up with a computational neuroscientist from the Frankfurt Institute of Advance Studies (FIAS) to shed new light on this important issue. Our central hypothesis is that early spontaneous patterns of activity exhibit an orderly columnar structure that forms the basis for building sensory evoked representations. Using the orientation preference map in ferret visual cortex as a model system, the team will employ novel techniques for expressing highly sensitive and persistent neural activity markers in visual cortex to perform chronic imaging of spontaneous and visually-evoked activity of large populations of neurons, starting a week prior to orientation map formation, up to its full maturation several weeks later. Using quantitative analysis of patterns of spontaneous activity, the team will characterize the structure of spontaneous activity in the early visual cortex and describe its relation to the mature orientation preference map. Constrained by the empirical results, a mathematical model will be built, aiming at providing a concise and accurate description of our spontaneous activity scaffolding hypothesis and to derive testable implications of this hypothesis. Through this project the researchers are expected to gain a quantitative understanding of how spontaneous and visually-driven activity interact to shape the early development of cortical circuitry. The research proposed here is expected to result in an improved understanding of early cortical development. Spontaneous activity potentially has a huge impact on developing cortical circuits and the proposed research aims at elucidating its role. It could reveal a previously unappreciated potential supporting role of spontaneous activity in forming sensory representations during early cortical development. Methodologically, the project will establish new experimental techniques that allow monitoring with unprecedented sensitivity the activity of large populations of neurons over extended periods of time, beginning at very early stages in development. It will provide novel methods for quantifying the spatiotemporal patterns of spontaneous and visual evoked population activity. Scientifically, the study will highlight the unanticipated richness and modular organization of early spontaneous activity in the cortex. In addition, the project will establish a new theory of visual cortical development that explicitly takes the rich nature of spontaneous activity into account. This theory will be strongly backed up by the empirical data. Beyond the new insights that will be gained about cortical development, the proposed research will have a broader impact in demonstrating the synergy that derives from combining state of the art experimental approaches, with novel techniques for data analysis and theoretical modeling. This project creates an interdisciplinary US-German collaboration between the FIAS and the MPFI. The results of this project will be broadly disseminated to the research community in journal publications, at conferences, and via a project website, and to the general public through presentations, outreach events and unique programs on both sides. Teaching and learning is promoted through programs for graduate, undergraduate, and high school students as well as engagement of post-baccalaureate participation in research activities. Finally, this project will contribute to a deeper understanding of the activity-dependent mechanisms that are responsible for the normal development of cortical circuits - fundamental knowledge that serves as the basis for novel treatments for a host of neurodevelopmental disorders that impact the quality of life for billions of people worldwide.